Molecular recognition is central to biological processes, from high-affinity protein-ligand interactions to the more transient protein-protein recognition events of signal transduction pathways. Such events depend on the versatility of proteins, which have been adapted to new roles as organisms have evolved. As an example, to capture a foreign antigen, a small number of antibodies from the immune system's naïve library (which contains approximately 107 variants) (1) recognize the antigen and bind to it with moderate affinity. Selection and maturation then introduces further mutations to generate the tight, highly specific binding required to eliminate the antigen. In this way a staggering array of binding modes can be grafted on to the basic antibody scaffold, to sequester targets varying from small molecules to whole cells.
This strategy can be replicated in the laboratory to produce very large libraries of antibody variants (>1010 different clones) (2,3) that can then be selected for binding to a particular target. Repeated cycles of amplification and selection for binding can then “discover” the test-tube antibodies with tight and specific molecular binding characteristics. This in vitro approach can also be applied to other scaffolds. For example, randomization and selection by phage display have been used to study and improve the binding of growth hormone and the growth factor heregulin to their respective receptors (4,5), and “affibodies” have been developed from libraries of a three-helix bundle domain from staphylococcal protein A (6,7). This general area has been the subject of several reviews (8-10).
OB-fold domains are generally small structural motifs found in a variety of proteins and originally named for their oligonucleotide/oligosaccharide binding properties. The OB-fold domain is a five-stranded closed  barrel and the majority of OB-fold domains proteins use the same face for ligand binding or an as active site. Different OB-fold domains use this “fold-related binding face” to bind oligosaccharides, oligonucleotides, proteins metal ions and catalytic substrates. OB-fold domains are described in for example, Arcus, Curr. Opin. Strict. Biol., Vol. 12: 794-801 (2002) and Theobald, Annu. Rev. Biophys. Biomol. Struct., Vol., 32: 115-33 (2003). Canadian Patent Publication No. 2,378,871 describes beta-pleated sheet proteins with binding properties.
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